SUO 2018: A Statistical Analyses of the PROSPER Study by Prior Definitive Surgery

Phoenix, Arizona (UroToday.com) Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) are at high risk of developing metastatic CRPC. Metastases development is associated with rising PSA and PSA doubling time of less than 10 months. Therefore, the goal of nmCRPC treatment is to delay metastatic disease progression, delay initiation of additional antineoplastic therapies, and thus prolong survival with maximizing the quality of life. Enzalutamide has been shown to be superior to bicalutamide in improving radiographic progression free survival in a subgroup of patients with nmCRPC in the STRIVE trial.1  In the primary analysis of the PROSPER study2, enzalutamide provided a statistically significant and clinically meaningful improvement in metastasis-free survival (MFS) in men with nmCRPC. In this additional analysis of the PROSPER trial, patients were stratified by whether they had prior definitive therapy (surgery/radiation) or not.

In the PROSPER study, eligible patients with nmCRPC, with a PSA doubling time ≤ 10 months, and a PSA ≥ 2 ng/mL at screening, continued androgen deprivation therapy and were randomized 2:1 to either enzalutamide 160 mg or placebo. The primary endpoint was MFS. The study design is shown in figure 1.

SUO 2018 poster 201 figure 1 study design

Overall 1401 patients were enrolled, with a median age of 74 years. Table 1 demonstrates the demographic and baseline patient characteristics.

SUO 2018 poster 201 table 1 pt characteristics

In all patients, enzalutamide reduced the risk of metastasis or death by 71% (HR 0.29; 95% CI: 0.24-0.35; p < .0001). A total of 391 patients (28%) had prior definitive surgery, including prostatectomy and cryoablation (n = 246 [26%] in the enzalutamide group, n = 145 [31%] in the placebo group). Notably, Enzalutamide significantly reduced the risk of metastasis or death regardless of whether patients received prior definitive surgery (HR with prior surgery, 0.18; 95% CI: 0.13-0.26; HR without prior surgery, 0.37; 95% CI, 0.30-0.47), as can also be seen in table 2.

SUO 2018 poster 201 table 2 met free survival surgery

Enzalutamide also reduced the risk of metastases or death regardless of whether patients received prior definitive radiotherapy, as can be seen in table 3. The treatment effect was greater in those who received prior radiotherapy.

SUO 2018 poster 201 table 3 met free survival radiotherapy

The authors concluded that in patients with nmCRPC and PSA doubling time less than 10 months, enzalutamide treatment resulted in a clinically and statistically meaningful reduction of metastases development or death. This remained constant regardless of whether patients had received prior definitive therapy (surgery or radiation).

Presented by: Paul R. Sieber, MD, FACS, Lancaster Urology, Lancaster, Pennsylvania

References:
1.  Smith MR et al. JCO 2013
2.  Hussain M. et al. NEJM 2018

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona
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